NDLI: Transforming Growth Factor β and Insulin Signal Changes in Stromal Fibroblasts of Individual Keratoconus Patients

Content Provider	PubMed Central
Author	Foster, James Wu, Wai-hong Scott, Sherri-gae Bassi, Mehak Mohan, Divya Daoud, Yassine Stark, Walter J. Jun, Albert S. Chakravarti, Shukti
Editor	Connon, Che John
Copyright Year	2014
Abstract	Keratoconus (KC) is a complex thinning disease of the cornea that often requires transplantation. The underlying pathogenic molecular changes in this disease are poorly understood. Earlier studies reported oxidative stress, metabolic dysfunctions and accelerated death of stromal keratocytes in keratoconus (KC) patients. Utilizing mass spectrometry we found reduced stromal extracellular matrix (ECM) proteins in KC, suggesting ECM-regulatory changes that may be due to altered TGFβ signals. Here we investigated properties of stromal cells from donor (DN) and KC corneas grown as fibroblasts in serum containing DMEM: F12 or in serum-free medium containing insulin, transferrin, selenium (ITS). Phosphorylation of SMAD2/3 of the canonical TGFβ pathway, was high in serum-starved DN and KC fibroblast protein extracts, but pSMAD1/5/8 low at base line, was induced within 30 minutes of TGFβ1 stimulation, more so in KC than DN, suggesting a novel TGFβ1-SMAD1/5/8 axis in the cornea, that may be altered in KC. The serine/threonine kinases AKT, known to regulate proliferation, survival and biosynthetic activities of cells, were poorly activated in KC fibroblasts in high glucose media. Concordantly, alcohol dehydrogenase 1 (ADH1), an indicator of increased glucose uptake and metabolism, was reduced in KC compared to DN fibroblasts. By contrast, in low glucose (5.5 mM, normoglycemic) serum-free DMEM and ITS, cell survival and pAKT levels were comparable in KC and DN cells. Therefore, high glucose combined with serum-deprivation presents some cellular stress difficult to overcome by the KC stromal cells. Our study provides molecular insights into AKT and TGFβ signal changes in KC, and a mechanism for functional studies of stromal cells from KC corneas.
Related Links	http://dx.doi.org/10.1371/journal.pone.0106556
Starting Page	106556
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	9
Language	English
Publisher	Public Library of Science
Publisher Date	2014-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Correction: Transforming Growth Factor β and Insulin Signal Changes in Stromal Fibroblasts of Individual Keratoconus Patients

Transforming Growth Factor β Signaling Overcomes Dasatinib Resistance in Lung Cancer

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Accelerated Wound Closure In Vitro by Fibroblasts from a Subgroup of Cleft Lip/Palate Patients: Role of Transforming Growth Factor-α

Activation of the Connective Tissue Growth Factor (CTGF)-Transforming Growth Factor β 1 (TGF-β 1) Axis in Hepatitis C Virus-Expressing Hepatocytes

EBP1 Is a Novel E2F Target Gene Regulated by Transforming Growth Factor-β

Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia

A Soluble Factor from Trypanosoma cruzi Inhibits Transforming Growth Factor-ß-Induced MAP Kinase Activation and Gene Expression in Dermal Fibroblasts

Transforming Growth Factor β1 Induces the Expression of Collagen Type I by DNA Methylation in Cardiac Fibroblasts

Transforming Growth Factor β and Insulin Signal Changes in Stromal Fibroblasts of Individual Keratoconus Patients

Similar Documents

Correction: Transforming Growth Factor β and Insulin Signal Changes in Stromal Fibroblasts of Individual Keratoconus Patients

Transforming Growth Factor β Signaling Overcomes Dasatinib Resistance in Lung Cancer

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Accelerated Wound Closure In Vitro by Fibroblasts from a Subgroup of Cleft Lip/Palate Patients: Role of Transforming Growth Factor-α

Activation of the Connective Tissue Growth Factor (CTGF)-Transforming Growth Factor β 1 (TGF-β 1) Axis in Hepatitis C Virus-Expressing Hepatocytes

EBP1 Is a Novel E2F Target Gene Regulated by Transforming Growth Factor-β

Dysregulation of the Transforming Growth Factor β Pathway in Induced Pluripotent Stem Cells Generated from Patients with Diamond Blackfan Anemia

A Soluble Factor from Trypanosoma cruzi Inhibits Transforming Growth Factor-ß-Induced MAP Kinase Activation and Gene Expression in Dermal Fibroblasts

Transforming Growth Factor β1 Induces the Expression of Collagen Type I by DNA Methylation in Cardiac Fibroblasts

Transforming Growth Factor β and Insulin Signal Changes in Stromal Fibroblasts of Individual Keratoconus Patients